What is the use of tramadol (opioid analgesic)?

From the Guidelines

Tramadol should be used with caution and at the lowest possible dose, with a maximum daily dose of 400 mg for immediate-release formulations and 300 mg for extended-release formulations, due to its potential risks and side effects, as recommended by the most recent guidelines 1.

Tramadol Mechanism and Usage

Tramadol is a weak mu-opioid receptor agonist with some norepinephrine and serotonin reuptake inhibition, used for treating moderate to moderately severe pain. It is available as immediate-release and extended-release formulations. The usual adult dosage ranges from 50-100 mg every 4-6 hours as needed for pain.

Important Considerations

• Tramadol should be used cautiously with other medications that affect serotonin due to the risk of serotonin syndrome.
• It should be tapered gradually when discontinuing after prolonged use to avoid withdrawal symptoms.
• Common side effects include dizziness, nausea, constipation, headache, and drowsiness.
• Tramadol carries risks of dependence, addiction, and respiratory depression, though generally less than stronger opioids.

Guidelines and Recommendations

The NCCN panel recommends a maximum daily dose of 400 mg for IR formulations and 300 mg for ER formulations for adults with normal hepatic and renal function 1. Lower doses are recommended for older adults and those with hepatic and/or renal dysfunction to reduce the risk of seizures.

Comparison with Other Opioids

Tramadol is less potent than other opioids and is considered to be approximately one-tenth as potent as morphine 1. A Cochrane review of tramadol concluded that limited evidence supports the use of tramadol for treatment of cancer pain and that tramadol is likely not as effective as morphine in this setting 1.

Recent Guidelines

The 2019 American College of Rheumatology guideline for the management of osteoarthritis conditionally recommends tramadol over non-tramadol opioids 1. However, the guideline also notes that evidence suggests very modest benefits of long-term opioid therapy and a high risk of toxicity and dependence.

From the FDA Drug Label

CLINICAL PHARMACOLOGY PHARMACODYNAMICS Tramadol Hydrochloride contains tramadol, a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of re-uptake of norepinephrine and serotonin Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to μ-opioid receptors.

Tramadol Mechanism of Action:

• Tramadol is a centrally acting synthetic opioid analgesic.
• Its mechanism of action involves binding to μ-opioid receptors and weak inhibition of re-uptake of norepinephrine and serotonin.
• The opioid activity is due to both the parent compound and the O-demethylated metabolite M1.
• M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding 2.

Key Points:

• Tramadol has a unique mechanism of action that involves both opioid and non-opioid pathways.
• The drug's analgesic effects are mediated by its binding to μ-opioid receptors and its ability to inhibit the re-uptake of norepinephrine and serotonin.
• The M1 metabolite plays a significant role in the drug's analgesic effects, with a higher potency than the parent compound.

From the Research

Tramadol Overview

• Tramadol is a centrally acting weak μ-opioid receptor analgesic, used to relieve moderate to severe pain management in patients 3, 4.
• It is a racemic mixture of (+)-tramadol and (-)-tramadol enantiomers, with the (+)-tramadol having greater affinity for μ-opioid receptor and providing additional prevention of 5-hydroxytryptamine reuptake 4.
• Tramadol does not show much serious adverse effects without any dependency potential in therapeutic doses, as seen in other opioids like morphine 4.

Tramadol Mechanism and Safety

• Tramadol's mode of action combines a weak opioid and a monoaminergic mode of action, distinguishing it from other opioids 3.
• It induces fewer opioid adverse reactions for a given level of analgesia compared with traditional opioids, with common adverse reactions such as nausea and dizziness usually occurring only at the beginning of therapy and attenuating over time 3.
• Tramadol has a low risk of abuse because it has only a weak opioid effect and its monoaminergic action could inhibit the development of dependence 3.

Tramadol Combinations and Usage

• Tramadol is often combined with other agents, such as paracetamol, to offer additive or synergistic benefits in treating multiple mechanisms of pain 5.
• Fixed-dose combination analgesics, such as tramadol and paracetamol, may be effective in treating pain while reducing toxicity due to lower doses 5.
• Tramadol is used worldwide and is listed in many medical guidelines for pain management, with its usage and combinations continuing to evolve 4, 5.

Alternative Therapies for Pain Management

• Mind-body therapies, such as meditation, hypnosis, and cognitive behavioral therapy, have been shown to be associated with moderate improvements in pain and small reductions in opioid dose 6.
• These therapies may be useful in addressing the opioid crisis and providing alternative options for pain management 6.
• However, the clinical effect of change in scores and the association of mind-body therapies with opioid-related outcomes require further study 7, 6.